Cross-reactive CD4 <sup>+</sup> T cells enhance SARS-CoV-2 immune responses upon infection and vaccination
Lucie Loyal, Julian Braun, Larissa Henze, Beate Kruse, Manuela Dingeldey, Ulf Reimer, Florian Kern, Tatjana Schwarz, Maike Mangold, Clara Unger, Friederike Dörfler, Shirin Kadler, Jennifer Rosowski, Kübrah Gürcan, Zehra Uyar‐Aydin, Marco Frentsch, Florian Kurth, Karsten Schnatbaum, Maren Eckey, Stefan Hippenstiel, Andreas C. Hocke, Marcel A. Müller, Birgit Sawitzki, Stefan Miltenyi, Friedemann Paul, Marcus Mall, Holger Wenschuh, Sebastian Voigt, Christian Drosten, Roland Lauster, Nils Lachman, Leif Erik Sander, Victor M. Corman, Jobst Röhmel, Lil Meyer‐Arndt, Andreas Thiel, Claudia Giesecke‐Thiel
Abstract
T cells are ubiquitous but decrease with age. We identified a universal immunodominant coronavirus-specific spike peptide (S816-830) and demonstrate that preexisting spike- and S816-830–reactive T cells were recruited into immune responses to SARS-CoV-2 infection and their frequency correlated with anti–SARS-CoV-2-S1-IgG antibodies. Spike–cross-reactive T cells were also activated after primary BNT162b2 COVID-19 messenger RNA vaccination and displayed kinetics similar to those of secondary immune responses. Our results highlight the functional contribution of preexisting spike–cross-reactive T cells in SARS-CoV-2 infection and vaccination. Cross-reactive immunity may account for the unexpectedly rapid induction of immunity after primary SARS-CoV-2 immunization and the high rate of asymptomatic or mild COVID-19 disease courses.